The overarching goal of this project is to identify and characterize genetic determinants of nicotine dependence in a large African-American population. This proposal builds on the foundation laid in the COLLABORATIVE GENETIC STUDY OF NICOTINE DEPENDENCE (COGEND), in which we studied nicotine-dependent cases and non- dependent smoking controls of European descent in a genome wide association study and a comprehensive candidate gene study (Bierut et al., 2007; Saccone et al., 2007). This project proposes to ascertain and assess a well defined African American case control sample in order to conduct robust genome-wide association and candidate gene studies. In COGEND we also recruited more than 757 African Americans (498 nicotine dependent cases and 259 non-dependent smoking controls) whom we will combine with the sample we propose to collect here for genetic analyses. Importantly, the procedures for recruitment and phenotypic measurement are similar to our previous studies (COGEND) and so this sample can be combined and compared with our genetic studies of nicotine dependence in an European American sample and other projects of nicotine dependence that have been collected by other investigators. There are 4 specific aims in this project: Aim 1: To perform a telephone screening of a targeted community sample (N=100,000) for smoking-related behavior in order to ascertain 1,000 African American nicotine-dependent cases and 1,000 African American non-dependent smoking controls. Aim 2: To comprehensively assess, through a personal interview, 1,000 African American nicotine dependent cases and 1,000 African American non-dependent smoking controls. Aim 3: To evaluate genetic associations for nicotine dependence in the 1,498 nicotine-dependent cases and 1,259 non-dependent smoking controls resulting from combination of the present sample with the COGEND African American sample. Aim 4: To expand the genetic epidemiologic and association studies to examine refined phenotypes of nicotine dependence and correlated characteristics. Efforts to identify genetic variants that increase the risk for nicotine dependence are beginning to yield important results which hold the promise of tailored risk assessment, and more effective, targeted smoking cessation treatments. The proposed study of African Americans will address the disparity in research priorities, provide an opportunity to identify novel genetic risk factors for nicotine dependence, confirm existing findings, and improve our understanding of potential genetic risk factors for characteristics correlated with nicotine dependence in this underserved population.